Ground-breaking molecular imaging studies have visualized gene expression, biochemical reactions, signal transduction and regulatory pathways in living cells and whole organisms in vivo. The Washington University Molecular Imaging Center directs major efforts into fundamental, translational and clinical research under the theme of imaging signal transduction and therapeutics in cancer using novel techniques and probes in combination with genetically-encoded reporters to pinpoint molecular events within target cells. The Washington University Molecular Imaging Center activities have spurred an explosion of collaborative, interdisciplinary research projects that have formed the foundation for exciting new directions in molecular imaging. A dedicated team of investigators have demonstrated an exceptional record of collaboration outside their own disciplines leading to an escalating interest in applying novel geneticallyencoded reporter strategies that allow the molecular characterization of cancer in vivo for basic research as well as diagnostic and prognostic clinical applications. In particular, this has lead to a major theme to study regulated signal transduction and protein processing in living organisms. The principal research projects address imaging of Notch signaling in cancer, investigate metabolic stress and checkpoint controls as targets for anticancer therapy, investigate the interaction of inflammation and viral-induced tumorigenicity in doubly transgenic reporter mice, and monitor trafficking of genetically-modified cells with PET during epigenetic modulation of donor lymphocytes in a clinical study of patients undergoing bone marrow transplant. The program also includes three molecular imaging scientific resources: the molecular imaging reporter core, chemistry core and high throughput screening robotics core, founded on molecular imaging platforms for readout of a wide range of bio-assays, including siRNA library screens, and chemical genetics. Our Molecular Imaging Center also provides a pilot project program for new investigators and a multidisciplinary training program for students, post-docs, and fellows.